Structural Considerations in Liposomal Anticancer Drug Delivery: Bilayer Organization, Drug Loading, and Retention Strategies

초록

The therapeutic potential of cytotoxic anticancer drugs is fundamentally governed by their spatiotemporal distribution, yet achieving precise control over drug behavior remains a central challenge in oncology. Liposomal formulations address this by providing a structurally adaptable platform capable of imposing pharmacokinetic control beyond the limitations of passive tumor accumulation. This review integrates the structural determinants of liposomal performance into a unified framework, evaluating how phospholipid bilayer composition and phase behavior establish primary membrane integrity. The roles of structural modulators—specifically cholesterol and PEG-lipids—are assessed for their capacity to refine bilayer packing and stabilize the biological interface. Preparation methods and drug-loading processes are further examined as the critical stages where these structural attributes are physically realized. This framework characterizes drug retention as a structural outcome emergent from molecular mobility constraints within the vesicle. While bilayer-level design regulates trans-membrane permeability, the present analysis underscores the complementary role of internal structural constraints arising from organized internal domains and matrix-like environments. By linking these multi-layered constraints to the pharmacological requirements of time-dependent cytotoxic drugs, this structural perspective provides a coherent basis for understanding how integrated liposomal design can strategically regulate molecular mobility to tailor release profiles and enhance anticancer efficacy.

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